Accelerated wound healing and its promoting effects of topical codeine on the healing of full-thickness cutaneous wound, evidences for modulating cytokines involved in pain, inflammation and collagen biosynthesis.

Abstract

The inflammation and pain occur in all the wounds. Opioids drugs decrease pain and may act as an anti-inflammation. The current study was conducted to investigate the efficiency of the topical uses of Codeine on full-thickness excision wound models by focusing on relationship between pain mediators, inflammation and wound healing rate. Following the induction of anesthesia, a skin wound with a size of 7-mm punch was induced on the dorsal surfaces of each mouse. The mice were divided into five categories: groups I-III were daily administered 2.5%, 5%, and 10% Codeine gel; those in group IV were administered phenytoin cream, and group V (controls) received base ointment. To assess the effects of Codeine gel on the wound healing process, the wound area, histological parameters, and the relative protein expression of CXCR1, CXCR2, IL-6, IL-6R, PDGF, PDGFR, and COL1A along with the plasma concentrations of IL-1β, IL-10, and TNF-α were investigated on days 3, 7, and 14. On days 7 and 14, the wound area was significantly lower in the treated mice compared to the controls (P < 0.05). Angiogenesis, collagen deposition, and epithelium thickness were significantly higher in the treatment groups compared to the control group (P < 0.05). The relative protein expressions of CXCR1, CXCR2, IL-6, and IL-6R and the plasma concentrations of IL-1β and TNF-α were significantly lower in the treated groups. Meanwhile, the relative protein expressions of PDGF, PDGFR, and COL1A and the plasma concentration of IL-10 were significantly higher in the treated mice (P < 0.05). Administration of Codeine gel accelerated wound healing through decreasing the pain mediators, inflammation and promoting proliferative phase.